A series of experiments were carried out to investigate the role and function of regulatory T cells in modulating the activation of B cells to antibody production. It was first demonstrated that high concentrations of free carrier inhibit the MHC-restricted activation of B cell responses. This inhibition was shown to be mediated by regulatory T cells functioning through two distinct pathways distinguishable by the involvement of different Lyt-defined T cell subpopulations. Both pathways were MHC-restricted and antigen-specific in their activation requirements. An Lyt 1+2- population functioned through an antigen non-specific effector pathway requiring the participation of an Lyt 1-2+ unprimed T cell. An Lyt 1-2+ T cell functioned through an antigen-specific and MHC restricted effector pathway without requirement for participation of additional T cells. Monoclonal T cell suppressor populations have recently been derived and are currently being evaluated.